Understanding the mechanisms that control the formation, morphogenesis, and differentiation of mesodermal tissues such as the heart, skeletal muscles, and visceral organs is of major importance not only from a basic science point of view but also from a human health perspective. The process of mesodermal tissue development in the genetic model Drosophila has proved to be an ideal system to study these mechanisms, many of which have been strikingly conserved between invertebrates and vertebrates. Previous work in this system has shown that specific combinations of ectodermally derived signals and mesoderm-intrinsic competence factors are required to induce specific tissues in defined areas within the mesoderm. Subsequent signals from within the mesoderm help to refine these domains and generate the progenitors of individual mesodermal cell types. Our current proposal aims to dissect (in aim 1) the stage- and tissue-specific functions of a mesoderm-intrinsic regulator, tinman, which is a key mediator of signals during the induction of cardiac, dorsal somatic, and visceral muscle progenitors and, potentially, acts in cardiac patterning. We will also define (in aim 2) new mechanisms that integrate intrinsic and extrinsic inputs during mesodermal tissue induction. In particular, we aim to clarify the specific mechanism by which Wingless signals, in combination with the BMP-type of signal Dpp and tinman, induce cardiac and dorsal somatic muscle progenitors through the effector Pangolin. Further, we plan to identify and characterize an unknown repressor, which acts to prevent the induction of mesodermal genes by Dpp in the ectoderm. We will also examine how signals from the somatic mesoderm, which are mediated by Jelly Belly and its receptor Anaplastic Lymphoma Kinase, cooperate with visceral mesoderm-specific competence factors to induce visceral muscle progenitors. In aim 3, we will define the developmental and molecular functions of the newly characterized Dorsocross T-box genes, which are induced by Dpp plus Wingless in mesodermal areas generating cardiac and dorsal somatic muscle progenitors, and later are expressed in cardiac inflow valves. Finally, in aim 4 we will utilize our detailed knowledge of the enhancers structures from genes that are induced in the dorsal mesoderm in a bioinformatics-based screen to identify novel targets of combinatorial inputs in the dorsal mesoderm. Altogether, these approaches will provide general insights into how combinations of extrinsic and intrinsic cues are integrated to elicit the exquisite developmental responses that lead to the formation and morphogenesis of distinct mesodermal tissues and organs. We anticipate that this information will continue to provide important clues to the understanding of mesodermal tissue development in vertebrates as well as the causes of human disease such as congenital heart abnormalities and organ defects. [unreadable] [unreadable]